Transplant Cell Ther
October 2024
Aims: To investigate the mechanism of exosomes' role in the transformation of MDS to AML.
Methods: Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry.
Myelofibrosis (MF) is a disorder characterized by the proliferation of myeloid precursors, commonly due to overactive JAK signaling. The discovery of the JAK2 mutation and subsequent development of JAK inhibitors (JAKi) results in reduced spleen size, improved symptom, and enhanced survival in MF patients. However, there are unmet needs of additional novel targeted therapies for this incurable disease due to the limited utility of first-generation JAKis, which are associated with dose-limiting cytopenia and disease recurrence.
View Article and Find Full Text PDFBackground: Umbilical cord blood hematopoietic stem cells are commonly used for hematopoietic system reconstitution in recipients after umbilical cord blood transplantation (UCBT). However, the optimal conditioning regimen for UCBT remains a topic of debate. The exact impact of total body irradiation (TBI) as a part of conditioning regimens remains unknown.
View Article and Find Full Text PDFBackgrounds: Chimeric antigen receptor (CAR)-T cell therapy has achieved unprecedented success in treating hematopoietic malignancies. However, this cell therapy is hampered in treating acute myeloid leukemia (AML) due to lack of ideal cell surface targets that only express on AML blasts and leukemia stem cells (LSCs) but not on normal hematopoietic stem cells (HSCs).
Methods: We detected the CD70 expression on the surfaces of AML cell lines, primary AML cells, HSC, and peripheral blood cells and generated a second-generation CD70-specific CAR-T cells using a construct containing a humanized 41D12-based scFv and a 41BB-CD3ζ intracellular signaling domain.
Hodgkin lymphoma (HL) is a hematologic malignancy that comprises about 10% of all lymphomas with the most common type being classical HL (cHL). The typical clinical presentation of cHL involves multiple region lymphadenopathy and a chest mass found on imaging. However, not all patients present with the typical symptomology of cHL which poses a diagnostic challenge.
View Article and Find Full Text PDFClassical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.
View Article and Find Full Text PDFAcute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone.
View Article and Find Full Text PDFTher Adv Hematol
February 2022
The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of through a chromosome (11;14) translocation. MCL international prognostic index (MIPI), proliferation index, and mutation status are currently utilized for prognostication.
View Article and Find Full Text PDFPhosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpoint was unveiled in leukemic patient cells and cell lines.
View Article and Find Full Text PDFAntibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, "off-the-shelf" universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting.
View Article and Find Full Text PDFImmune thrombocytopenic purpura (ITP) is a hematological disorder characterized by immune-mediated destruction of platelets that could be triggered by a number of causes. ITPs are usually treated with steroid, immunomodulators or immunosuppressors, and intravenous immunoglobulin therapy though refractory/relapsed status frequently occurs. It was suggested that autologous hematopoietic stem cell transplant (HSCT) after high-dose chemotherapy conditioning might improve ITP patients' peripheral blood platelet counts via reorganizing disrupted immune balance in the hematopoietic and hematologic systems.
View Article and Find Full Text PDFPolyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3'-untranslated region (3'-UTR) specific sequence signal. APA processing can generate several mRNA isoforms from a single gene, which may have different biological functions on their target gene.
View Article and Find Full Text PDFHydroxyurea (HU) has been widely used in sickle cell disease. Its potential long-term risk for carcinogenesis or leukemogenic risk remains undefined. Here, we report a 26 y old African-American female with Sickle Cell Disease (SCD) who developed refractory/relapsed acute myeloid leukemia (AML) 6 months after 26 months of HU use.
View Article and Find Full Text PDFMantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology.
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